Krishnamurthy Venkatagiri, Paredes Spir Isabella, Mammino Kevin M, Nocera Joe R, McGregor Keith M, Crosson Bruce A, Krishnamurthy Lisa C
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States.
Department of Neurology, Emory University, Atlanta, GA, United States.
Front Psychiatry. 2022 Jun 9;13:923076. doi: 10.3389/fpsyt.2022.923076. eCollection 2022.
Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain's major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamate-glutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABAGlxCBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA*Glx interaction was the common denominator across both groups, but younger participants' brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no group-specific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks.
老年人通常会经历认知功能的衰退，但身体健康和生活方式的改善在人的整个生命周期中都可能具有神经保护作用。本研究的主要目的是深化我们对心肺适能和神经生理属性如何与认知衰退相关的基本理解。虽然脑血流量（CBF）对于向组织供应营养至关重要，但大脑的主要神经递质（即γ-氨基丁酸，GABA，以及谷氨酸-谷氨酰胺复合物，Glx）与氧化代谢密切相关。在血流-代谢耦合的背景下，关键问题是这些神经生理参数如何相互作用，导致认知衰退。此外，心肺适能如何影响衰老的神经生理学和认知尚不清楚。为了解决这些问题，我们招募了10名年轻和12名认知功能完好的老年人，使用磁共振波谱（MRS）收集GABA和Glx，使用伪连续动脉自旋标记磁共振成像（MRI）收集CBF，使用YMCA亚极量测试测量VO2max作为心肺适能的指标，并使用一系列行为评估进行认知和运动认知测量。我们在额前叶一般区域的前辅助运动区（pre-SMA）观察到年轻和老年参与者之间GABA+、Glx和CBF的预期差异。当通过多元线性回归将GABA+和Glx与CBF相关联时，Glx被确定为模型的主要贡献因素。对于高阶执行功能（即抑制与颜色命名），GABAGlxCBF相互作用在年轻人中至关重要，而在老年参与者中仅涉及Glx。对于单手运动灵活性，GABA*Glx相互作用是两组的共同特征，但年轻参与者的大脑也涉及CBF。在选择性运动抑制方面，年轻参与者的CBF是唯一主要的神经生理因素。在适能方面，将两组人群合并后，心肺适能与GABA、Glx和运动表现显著相关，但未观察到特定组别的关系。综上所述，我们的结果表明，Glx和CBF耦合随着年龄增长而降低，这可能是由于胶质细胞氧化代谢改变所致。我们的数据表明，对于对衰老敏感的不同认知测量，GABA、Glx和CBF的参与和权重不同，更高的适能允许更有效的代谢转变，从而促进认知-运动任务表现的改善。
